Author + information
- Received October 22, 2019
- Revision received December 23, 2019
- Accepted December 24, 2019
- Published online May 25, 2020.
- Muthiah Vaduganathan, MD, MPHa@mvaduganathan,
- Gregg C. Fonarow, MDb@gcfmd,
- Stephen J. Greene, MDc@SJGreene_md,
- Adam D. DeVore, MD, MHSc@_adevore,
- Abhishek Kavati, PhD, MBA, MSd,
- Slaven Sikirica, MScd,
- Nancy M. Albert, PhDe,
- Carol I. Duffy, DOd,
- C. Larry Hill, PhDc,
- J. Herbert Patterson, PharmDf,
- John A. Spertus, MD, MPHg@jspertus,
- Laine E. Thomas, PhDh@texhern,
- Fredonia B. Williams, EdDi,
- Adrian F. Hernandez, MD, MHSc and
- Javed Butler, MD, MPH, MBAj,∗ (, )@JavedButler1
- aBrigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, Boston, Massachusetts
- bAhmanson-UCLA Cardiomyopathy Center, University of California Los Angeles, Los Angeles, California
- cDuke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
- dNovartis Pharmaceuticals Corporation, East Hanover, New Jersey
- eNursing Institute and Kaufman Center for Heart Failure, Cleveland Clinic, Cleveland, Ohio
- fEshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina
- gSaint Luke’s Mid America Heart Institute and University of Missouri-Kansas City, Kansas City, Missouri
- hDuke Clinical Research Institute and Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina
- iMended Hearts, Huntsville, Alabama
- jDepartment of Medicine, University of Mississippi Medical Center, Jackson, Mississippi
- ↵∗Address for correspondence:
Dr. Javed Butler, University of Mississippi Medical Center, Department of Medicine (L650), 2500 North State Street, Jackson, Mississippi 39216.
Objectives The purpose of this study was to characterize the clinical profile, treatment patterns, and clinical outcomes of patients with comorbid diabetes mellitus (DM) and heart failure with reduced ejection fraction (HFrEF) in a contemporary, real-world U.S. outpatient registry in the context of evolving treatment strategies.
Background Specific antihyperglycemic classes have differential risks and benefits with respect to HF. Limited data are available evaluating contemporary treatment patterns and outcomes of patients with comorbid DM and HFrEF.
Methods Among 4,970 patients with chronic HFrEF (≤40%) across 152 U.S. sites in the CHAMP-HF prospective, observational registry (2015 to 2017), we examined therapies and clinical outcomes by DM status.
Results Median age was 68 (58 to 75) years of age; 29% were women; 73.5% were white; and 64% had coronary artery disease. Overall, 42% (n = 2,085) had comorbid DM with a median hemoglobin A1c (HbA1c) level of 7.2% (interquartile range [IQR]: 6.4% to 8.3%). One-fourth of DM patients (24%) were not treated with an antihyperglycemic therapy. Most patients with DM were taking 1 (46%) or 2 (23%) antihyperglycemic therapies: metformin (40%); insulin (33%); sulfonylureas (24%); dipeptidyl peptidase-4 inhibitors (10%); glucagon-like peptide (GLP)-1 receptor agonists (4%); sodium-glucose cotransporter (SGLT)-2 inhibitors (2%); and thiazolidinediones (2%). Among patients with DM, 62%, 16%, 80%, and 33.5% were receiving any angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitor (ARNI), β-blockers, or mineralocorticoid receptor antagonists (MRAs) at baseline, respectively. Among patients without DM, corresponding baseline rates were 65%, 15%, 80%, and 37%, respectively. Patients with or without DM were infrequently treated with guideline-directed HFrEF therapies at target doses (≤27% across classes). During median 15-month follow-up, patients with DM experienced higher rates of all-cause mortality or HF hospitalization (30% vs. 23%, respectively), independent of 11 pre-specified covariates (adjusted hazard ratio: 1.35 (95% confidence interval: 1.21 to 1.52); p < 0.001).
Conclusions Despite higher risk-adjusted clinical event rates in patients with comorbid HFrEF and DM, guideline-directed medical therapies for both disease states are incomplete and represent an important target for quality improvement through multidisciplinary care pathways.
The CHAMP-HF registry was sponsored by Novartis Pharmaceuticals Corporation. Data were managed by United BioSource. The Duke Clinical Research Institute served as the data analytic center. Dr. Vaduganathan is supported by a KL2/Catalyst Medical Research Investigator training award from Harvard Catalyst U.S. National Institutes of Health [NIH]/National Center for Advancing Translational Sciences award UL 1TR002541; serves on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer AG, Boehringer Ingelheim, Cytokinetics, and Relypsa; and participates in clinical endpoint committees for studies sponsored by Novartis and the NIH. Dr. Fonarow has received research support from NIH; and is a consultant for Abbott, Amgen, Bayer, CHF Solutions, Janssen, Medtronic, and Novartis. Dr. Greene has received support from Heart Failure Society of America/Emergency Medicine Foundation Acute Heart Failure Young Investigator Award funded by Novartis; received research support from Amgen, Bristol-Myers Squibb, and Novartis; and serves on an advisory board for Amgen. Dr. DeVore has received research support from Akros Medical, American Heart Association, Amgen, Bayer, Intra-Cellular Therapies, Luitpold Pharmaceuticals, National Heart, Lung, Blood Institute, Novartis, and Patient-Centered Outcomes Research Institute (PCORI); and is a consultant for Novartis. Drs. Kavati and Duffy and Mr. Sikirica are employees of Novartis Pharmaceuticals Corporation. Dr. Albert is a consultant for Novartis and Boston Scientific. Dr. Patterson has received research support from Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, and Otsuka; and is a consultant for Novartis. Dr. Spertus is a consultant for Novartis, Bayer, AstraZeneca, United Healthcare, and Janssen; holds the copyright to the Kansas City Cardiomyopathy Questionnaire; has equity in Health Outcomes Sciences; and serves on the Board of Directors for Blue Cross-Blue Shield of Kansas City. Dr. Hernandez is a consultant for AstraZeneca, Bayer, Boston Scientific, Merck, and Novartis; and has received research support from American Regent, AstraZeneca, GlaxoSmithKline, Merck, Novartis, and Verily. Dr. Butler has received research support from NIH, Patient-Centered Outcomes Research Institute and the European Union; and is a consultant for Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol- Myers Squibb, CVRx, G3 Pharmaceutical, Innolife, Janssen, Luitpold, Medtronic, Merck, Novartis, Relypsa, StealthPeptide, SC Pharma, Vifor, and ZS Pharma. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Heart Failure author instructions page.
- Received October 22, 2019.
- Revision received December 23, 2019.
- Accepted December 24, 2019.
- 2020 American College of Cardiology Foundation
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